Original Article
Gene Therapy (2006) 13, 1545–1552. doi:10.1038/sj.gt.3302803; published online 1 June 2006
Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo
S Xenariou1,4, U Griesenbach1,4, S Ferrari1,4, P Dean1, R K Scheule2, S H Cheng2, D M Geddes1,4, C Plank3 and E W F W Alton1,4
- 1Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK
- 2Genzyme Corporation, Framingham, MA, USA
- 3Institute of Experimental Oncology, Technische Universität München, Munich, Germany
- 4UK Cystic Fibrosis Gene Therapy Consortium, UK
Correspondence: Dr U Griesenbach, Department of Gene Therapy, National Heart and Lung Institute, Imperial College, 1B Manresa Road, London SW3 6LR, UK. E-mail: u.griesenbach@imperial.ac.uk
Received 28 September 2005; Revised 19 April 2006; Accepted 20 April 2006; Published online 1 June 2006.
Abstract
We have assessed whether magnetic forces (magnetofection) can enhance non-viral gene transfer to the airways. TransMAGPEI, a superparamagnetic particle was coupled to Lipofectamine 2000 or cationic lipid 67 (GL67)/plasmid DNA (pDNA) liposome complexes. In vitro transfection with these formulations resulted in approximately 300- and 30-fold increase in reporter gene expression, respectively, after exposure to a magnetic field, but only at suboptimal pDNA concentrations. Because GL67 has been formulated for in vivo use, we next assessed TransMAGPEI in the murine nasal epithelium in vivo, and compared this to naked pDNA. At the concentrations required for in vivo experiments, precipitation of magnetic complexes was seen. After extensive optimization, addition of non-precipitated magnetic particles resulted in approximately seven- and 90-fold decrease in gene expression for naked pDNA and GL67/pDNA liposome complexes, respectively, compared to non-magnetic particles. Thus, whereas exposure to a magnetic field improved in vitro transfection efficiency, translation to the in vivo setting remains difficult.
Keywords:
magnetofection, physical methods, non-viral vectors, airway epithelium, cystic fibrosis
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